Changes of serum IgG glycosylation patterns in rheumatoid arthritis

Abstract

Background RA is a common chronic and systemic autoimmune disease, and the diagnosis is based significantly on autoantibody detection. This study aims to investigate the glycosylation profile of serum IgG in RA patients using high-throughput lectin microarray technology. Method Lectin microarray containing 56 lectins was applied to detect and analyze the expression profile of serum IgG glycosylation in 214 RA patients, 150 disease controls (DC), and 100 healthy controls (HC). Significant differential glycan profiles between the groups of RA and DC/HC as well as RA subgroups were explored and verified by lectin blot technique. The prediction models were created to evaluate the feasibility of those candidate biomarkers. Results As a comprehensive analysis of lectin microarray and lectin blot, results showed that compare with HC or DC groups, serum IgG from RA patients had a higher affinity to the SBA lectin (recognizing glycan GalNAc). For RA subgroups, RA-seropositive group had higher affinities to the lectins of MNA-M (recognizing glycan mannose) and AAL (recognizing glycan fucose), and RA-ILD group had higher affinities to the lectins of ConA (recognizing glycan mannose) and MNA-M while a lower affinity to the PHA-E (recognizing glycan Galβ4GlcNAc) lectin. The predicted models indicated corresponding feasibility of those biomarkers. Conclusion Lectin microarray is an effective and reliable technique for analyzing multiple lectin–glycan interactions. RA, RA-seropositive, and RA-ILD patients exhibit distinct glycan profiles, respectively. Altered levels of glycosylation may be related to the pathogenesis of the disease, which could provide a direction for new biomarkers identification.

Recent advances in N-glycan biomarker discovery among human diseases

“…They identified significantly decreased galactosylation in RA patients by evaluating the primary sequences of approximately 1400 oligosaccharides from 46 IgG samples. With the rapid development of novel characterization techniques in glycomics in the past decade, the reduction in IgG galactosylation levels in RA has been verified in dozens of studies, making it the first wellestablished glycan feature of RA [145,146]. In addition to reduced IgG galactosylation, other glycomic alterations, including decreased sialylation and increased fucosylation, were also observed in RA patients, as reviewed by Flevaris and Kontoravdi [100].…”

Cell Membrane Sialome: Sialic Acids as Therapeutic Targets and Regulators of Drug Resistance in Human Cancer Management

“…The altered glycosylation of IgG was strongly connected with pathogenesis and changes in the course of the disease [110]. It is of particular importance since it is widely known that altered sialylation in RA contributes to the regulation of arthritogenicity [111]. Lundström et al have suggested that changes in the glycome of serum can be considered potential indicators of MTX clinical response prediction [112].…”

Multiplexed Antibody Glycosylation Profiling Using Dual Enzyme Digestion and Liquid Chromatography-Triple Quadrupole Mass Spectrometry Method

“…Glycosylation occurring at the antibody Fc region has the potential to modify its binding affinity to innate immune receptors, thereby initiating signaling cascades that give rise to various antibody-dependent responses, such as inflammation, antibody-dependent cellular cytotoxicity, and antibody-dependent cellular phagocytosis ( 3 ). Given the critical biological functions associated with these responses, extensive studies have explored the association between Ig glycosylation and various diseases ( 4 , 5 , 6 , 7 ). Consequently, the development of sensitive and specific analytical methods for studying Ig glycopeptides has tremendous potential to uncover their biomedical impacts.…”